Ajioka Itsuki
Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo, 113-8510, Japan.
Dev Growth Differ. 2014 Jun;56(5):324-34. doi: 10.1111/dgd.12127. Epub 2014 Apr 3.
Once neurons enter the post-mitotic G0 phase during central nervous system (CNS) development, they lose their proliferative potential. When neurons re-enter the cell cycle during pathological situations such as neurodegeneration, they undergo cell death after S phase progression. Thus, the regulatory networks that drive cell proliferation and maintain neuronal differentiation are highly coordinated. In this review, the coordination of cell cycle control and neuronal differentiation during development are discussed, focusing on regulation by the Rb family of tumor suppressors (including p107 and p130), and the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitors. Based on recent findings suggesting roles for these families in regulating neurogenesis and neuronal differentiation, I propose that the Rb family is essential for daughter cells of neuronal progenitors to enter the post-mitotic G0 phase without affecting the initiation of neuronal differentiation in most cases, while the Cip/Kip family regulates the timing of neuronal progenitor cell cycle exit and the initiation of neuronal differentiation at least in the progenitor cells of the cerebral cortex and the retina. Rb's lack of involvement in regulating the initiation of neuronal differentiation may explain why Rb family-deficient retinoblastomas characteristically exhibit neuronal features.
在中枢神经系统（CNS）发育过程中，一旦神经元进入有丝分裂后的G0期，它们就会失去增殖潜能。当神经元在诸如神经退行性变等病理情况下重新进入细胞周期时，它们在S期进展后会发生细胞死亡。因此，驱动细胞增殖和维持神经元分化的调控网络是高度协调的。在这篇综述中，我们讨论了发育过程中细胞周期控制与神经元分化的协调，重点关注肿瘤抑制因子Rb家族（包括p107和p130）以及细胞周期蛋白依赖性激酶（Cdk）抑制剂Cip/Kip家族的调控作用。基于最近的研究结果表明这些家族在调节神经发生和神经元分化中的作用，我提出Rb家族对于神经元祖细胞的子代细胞进入有丝分裂后的G0期至关重要，且在大多数情况下不影响神经元分化的起始，而Cip/Kip家族至少在大脑皮层和视网膜的祖细胞中调节神经元祖细胞退出细胞周期的时间以及神经元分化的起始。Rb不参与调节神经元分化的起始，这可能解释了为什么Rb家族缺陷的视网膜母细胞瘤具有典型的神经元特征。
